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Bio-semiconductors are expected to be similar to organic semiconductors; however, they have not been utilized in application yet. In this study, we show the origin of electron appearance, N- and S-type negative resistances, rectification, and switching effects of semiconductors with energy storage capacities of up to 418.5 mJ/m 2 using granulated amorphous kenaf cellulose particles (AKCPs). The radical electrons in AKCP at 295 K appear in cellulose via the glycosidic bond C 1 -O 1 · -C 4 . Hall effect measurements indicate an n-type semiconductor with a carrier concentration of 9.89 × 10 15 /cm 3 , which corresponds to a mobility of 10.66 cm 2 /Vs and an electric resistivity of 9.80 × 10 2 Ωcm at 298 K. The conduction mechanism in the kenaf tissue was modelled from AC impedance curves. The light and flexible cellulose-semiconductors may open up new avenues in soft electronics such as switching effect devices and bio-sensors, primarily because they are composed of renewable natural compounds., (© 2024. The Author(s).)

We have developed a new neutron phase imaging system with a Talbot-Lau interferometer for utilization at the CN-3 port of the Kyoto University Reactor. To achieve efficient differential-phase imaging and visibility (dark-field) imaging at this beamline, we adopted a relatively shorter design wavelength of 2.7 Å. By fabricating neutron absorption gratings with thick gadolinium absorbers, we were able to obtain clear moiré fringes with a high visibility of 55% for thermal neutrons. As a demonstration of its imaging capabilities for expanded actual utilization in the medium-sized sources, we observed additively manufactured rods of Inconel 718. Using visibility imaging, we successfully examined variations in the size of defects in the rods caused by hot isostatic pressing process. In addition, we conducted tomography measurements of the rods, which allowed us to reveal the spatial distribution of defects at sub-micrometer scales., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Amyloidosis of the uterine cervix is rare. A 35-year-old pregnant woman underwent a cervical biopsy and was found to have amyloid deposits. The results of liquid chromatography-tandem mass spectrometry revealed that these deposits mainly consisted of immunoglobulin light chain (kappa chain). After undergoing several examinations, the patient was diagnosed with localized amyloidosis, without systemic or secondary amyloidosis. She underwent a normal delivery without disease exacerbation. The possible presence of systemic and secondary amyloidosis must be evaluated carefully during the diagnosis of localized cervical amyloidosis., (© 2020 Japan Society of Obstetrics and Gynecology.)

Aim: Our aim was to determine factors that affect maternal serum magnesium (Mg) levels, to help ensure the safety and efficacy of long-term magnesium sulfate (MgSO4 ) therapy for threatened preterm labor in singleton and twin pregnancies., Material and Methods: We retrospectively and arbitrarily studied 100 patients (singleton pregnancy, n = 65; twin pregnancy, n = 35) who received i.v. MgSO4 for >48 h for tocolysis of threatened preterm labor. We used multiple regression analysis to investigate the functional relations between the candidate factors and maternal serum Mg levels., Results: MgSO4 was administered as a loading dose of 3 g for 1 h followed by a maintenance dose of 1.0-2.0 g/h. There were no maternal severe adverse events related to the elevated Mg levels in any of the subjects. The results of multiple regression analysis revealed that total dose of MgSO4 for 24 h before blood collection (g/day), total serum protein level (g/dL), serum total calcium level (mg/dL), serum creatinine level (mg/dL) and maternal bodyweight (kg) significantly affected maternal serum Mg levels in both singleton and twin pregnancies (all P-values were < 0.001). Gestational age (weeks) and period of MgSO4 administration (days) at blood collection had no significant effect in singleton or twin pregnancies., Conclusion: Our study statistically shows that dose of MgSO4 , total serum protein level, serum total calcium level, serum creatinine level and maternal bodyweight are key factors to achieving safe and effective long-term tocolysis with MgSO4 in not only singleton but also twin pregnancies., (© 2015 The Authors. Journal of Obstetrics and Gynaecology Research © 2015 Japan Society of Obstetrics and Gynecology.)

There are two local subtypes of extravillous trophoblast (EVT): one is the proliferative phenotype of EVT, which primarily consists of proximal cells and the other is the invasive phenotype of EVT, which is composed mainly of distal cells of cell columns. The mechanism of invasion of EVT to the decidua remains obscure. In order to elucidate the potential role of apoptosis along the invasion of EVT to the decidua, we have assessed the expression of apoptosis-regulating proteins including Fas antigen (Fas), Fas-ligand (Fas-L) and Bcl-2 protein, and apoptosis in the proliferative phenotype of EVT and the invasive phenotype of EVT in term (37 to 38 wk) placenta Fas, Fas-L and Bcl-2 protein expression were examined by avidin/biotin immunoperoxidase method. Apoptosis was assessed by in situ DNA 3'-end labeling method. Appearance of apoptotic nuclei in EVT was also examined by transmission electron microscopy. Mean percentage of apoptosis-positive nuclei in the invasive phenotype of EVT was significantly higher than that in the proliferative phenotype of EVT. Transmission electron microscopy revealed the presence of apoptotic nuclei in the invasive phenotype of EVT. Immunohistochemical analyses revealed that Fas and Fas-L expression in the invasive phenotype of EVT were more abundant than those in the proliferative phenotype of EVT, while Bcl-2 protein expression in the invasive phenotype of EVT was less abundant than that in the proliferative phenotype of EVT. The present findings suggest that Fas/Fas-L and Bcl-2 protein expression participate in the regulation of apoptosis in EVT along the invasion to the decidua, and that the increased occurrence of apoptosis in the invasive phenotype of EVT may be attributable to the increased expressions of Fas and Fas-L and decreased expression of Bcl-2 protein in those cells in term placentas.

Objective: This study was undertaken to determine whether preeclampsia and intrauterine growth retardation are associated with an increase in placental apoptosis., Study Design: Tissue specimens from 7 normal term placentas and each of 7 term placentas complicated by severe preeclampsia or intrauterine growth retardation were analyzed. Fas antigen and Bcl-2 protein expression were examined by the avidin/biotin immunoperoxidase method, whereas apoptosis was assessed by the terminal deoxynucleotidyl transferase deoxy-UTP-nick end labeling (TUNEL) method and transmission electron microscopy., Results: Fas antigen was immunolocalized in syncytiotrophoblasts in all placentas examined. No changes in the intensity of Fas antigen immunostaining in syncytiotrophoblasts were apparent among those placentas. Bcl-2 protein was abundantly immunolocalized in syncytiotrophoblasts in normal term placentas, but least abundant in term placentas complicated by severe preeclampsia or intrauterine growth retardation. Apoptosis was apparent in the nuclei of both cytotrophoblasts and syncytiotrophoblasts. The apoptosis positive rate of syncytiotrophoblast nuclei in severe preeclamptic and intrauterine growth retardation term placentas was significantly higher than that in normal term placentas (severe preeclampsia, P <.001; intrauterine growth retardation, P <.01). Transmission electron microscopy revealed the appearance of apoptotic nuclei in trophoblasts in severe preeclamptic term placenta., Conclusion: Decreased expression of Bcl-2 protein in syncytiotrophoblasts in severe preeclamptic and intrauterine growth retardation placentas may result in the increase in apoptosis in syncytiotrophoblasts in those placentas.

Although tumor necrosis factor-alpha (TNFalpha) has been shown mainly to inhibit proliferation and induce apoptosis in a variety of cells, no information is available regarding whether human leiomyoma cells express TNFalpha. In the present study, we examined the expression of TNFalpha in leiomyomas, in comparison with that in the adjacent normal myometrium, using immunohistochemical staining and Western immunoblot analysis with a polyclonal antibody to human TNFalpha. Furthermore, we investigated the effect of sex steroid hormones on TNFalpha expression in leiomyoma cells cultured under serum-free, phenol red-free conditions. Immunohistochemical staining showed that TNFalpha expression in leiomyoma cells was higher than that in the adjacent normal myometrial cells, being more abundant in the proliferative phase than in the secretory, progesterone (P4)-dominated, phase of the menstrual cycle. TNFalpha expression in leiomyoma cells in pregnant uterus was scarce. Western immunoblot analyses of leiomyoma and normal myometrial tissue extracts revealed that TNFalpha, with a molecular mass of 17.3 kDa, was abundantly present in leiomyoma tissue extracts, relative to normal myometrial tissue extracts, and that TNFalpha expression in leiomyoma cells was most abundant in the proliferative phase of the menstrual cycle, less abundant in the secretory phase, and least abundant in pregnant uterus; whereas no such changes in TNFalpha expression were noted in the normal myometrium. In monolayer cultures of uterine leiomyoma cells under serum-free conditions, addition of P4 (3.18 x 10(-7) mol/L) resulted in a decrease in TNFalpha expression in the cells, relative to that in control cultures, whereas treatment with 17beta-estradiol (3.67 x 10(-8) mol/L) did not affect the TNFalpha expression in the cells. The concentrations of sex steroids used were within the physiological tissue concentrations noted in leiomyoma and myometrium. The present results suggest that the abundant expression of TNFalpha may be a molecular basis characteristic of leiomyomas in the human uterus and that P4 may play a vital role in down-regulating the expression of TNFalpha in human uterine leiomyoma.

In order to elucidate the regulation of human placental growth during pregnancy, we have assessed PCNA expression, apoptosis and Bcl-2 protein expression in placental trophoblasts over the course of pregnancy. PCNA, Bcl-2 protein and Fas antigen expression were examined by the avidin/biotin immunoperoxidase method, while apoptosis was assessed by in situ DNA 3'-end labeling method. Both PCNA expression and apoptotic DNA fragmentation were noted in cytotrophoblasts (C-cells), being most abundant in very early placenta, less abundant in midterm placenta and least abundant in term placenta. In contrast, Bcl-2 protein expression was noted in syncytiotrophoblasts (S-cells), being least abundant in very early placenta, less abundant in midterm placenta and most abundant in term placenta. These results indicate that very early placenta is characterized by highly proliferative activity of C-cells associated with increased occurrence of apoptosis. Since Bcl-2 protein is an apoptosis-inhibiting gene product, the minimal occurrence of apoptosis in term placenta seems likely to be attributable to the increased expression of Bcl-2 protein in S-cell in term placenta. On the other hand, in extravillous trophoblasts on cell columns, both PCNA and Bcl-2 protein expression were pronounced only in the shallower part, while Fas/Fas ligand expression and apoptosis were prominent in the deeper part. Thus, it seems likely that Bcl-2 protein expression also participates in the regulation of extravillous trophoblast apoptosis.

Uterine leiomyomas appear during the reproductive years and regress after menopause, indicating the ovarian steroid-dependent growth potential. Recently we have found that the use of levonorgestrel-releasing intrauterine system (IUS) is effective in the long-term contraception and management of menorrhagic women with uterine myomas because of a striking reduction in menorrhagia. These clinical experiences prompted us to characterize the effects of progestin on the proliferation and apoptosis of leiomyoma cells cultured in vitro. As epidermal growth factor (EGF) has been shown to mediate estrogen action and play a crucial role in regulating leiomyoma growth, we also investigated the effects of sex steroids on EGF and EGF receptor (EGF-R) expression in leiomyoma cells. In cultures of leiomyoma cells, the addition of either E(2) (10 ng/ml) or P(4) (100 ng/ml) resulted in an increase in proliferating cell nuclear antigen (PCNA) expression in the cells; whereas in cultures of normal myometrial cells, the addition of E(2) augmented PCNA expression in the cells, but P(4) did not. Immunoblot analysis revealed that leiomyoma cells contained immunoreactive EGF and that P(4) treatment resulted in an increase in EGF expression in the cells. In contrast, E(2) treatment augmented EGF-R expression in cultured leiomyoma cells, but P(4) did not. These results indicate that P(4) up-regulates the expression of PCNA and EGF in leiomyoma cells, whereas E(2) up-regulates the expression of PCNA and EGF-R in those cells. It is, therefore, conceivable that P(4) and E(2) act in combination to stimulate the proliferative potential of leiomyoma cells through the induction of EGF and EGF-R expression. We also found that Bcl-2 protein, an apoptosis-inhibiting gene product, was abundantly expressed in leiomyoma relative to that in normal myometrium, suggesting that the abundant expression of Bcl-2 protein in leiomyoma cells may be one of the molecular bases for the enhanced growth of leiomyoma relative to that of normal myometrium in the uterus. Furthermore, Bcl-2 protein expression in leiomyoma cells was up-regulated by P(4), but down-regulated by E(2). Therefore, it seems likely that P(4) may also participate in leiomyoma growth through the induction of Bcl-2 protein in leiomyoma cells.

In order to evaluate placental trophoblast proliferation and apoptosis during pregnancy, we investigated proliferating cell nuclear antigen (PCNA) expression, apoptosis and Bcl-2 protein expression in the human placenta using avidin/biotin immunoperoxidase method to examine PCNA and Bcl-2 protein expression, and TUNEL method to assess apoptosis. The appearance of apoptotic cells in very early term placental trophoblasts was also examined by transmission electron microscopy. PCNA was immunolocalized in the nuclei of cytotrophoblasts (C-cells). Determination of the mean percentage of PCNA-positive nuclei of C-cells revealed that PCNA expression in C-cells was highest in very early term (4th to 5th wk) placentas and significantly decreased with the advance of pregnancy. Bcl-2 protein was immunolocalized in the cytoplasm of syncytiotrophoblast (S-cell), being least abundant in very early term placentas, less abundant in early term and midterm placentas, and most abundant in term placentas. On the basis of TUNEL method, apoptosis was apparent in the nuclei of both C-cells and S-cell. The apoptosis positive rate of C-cell nuclei was highest in very early term 4th to 5th wk placentas, and significantly decreased in early term 7th to 9th wk and midterm placentas, but somewhat increased in term placentas compared to that in midterm placentas. On the other hand, apoptosis positive rate of S-cell nuclei was remarkably higher only in very early term 4th to 5th wk placentas compared to that in early term, midterm and term placentas. Transmission electron microscopy revealed the appearance of apoptotic nucleus in very early term placental trophoblasts. These results demonstrate for the first time that apoptosis in the human normal placenta predominates in both C-cells and S-cell in very early term 4th to 5th wk pregnancy and drastically diminished after 7th wk of pregnancy. An apparent increase in apoptosis in C-cells in term placentas compared to that in midterm placentas may reflect aging of the placenta or parturition-associated biological change. The abundant expression of Bcl-2 protein in S-cell in term placentas may be responsible for the diminished occurrence of apoptosis in S-cell in term placentas.

This study was conducted to analyze comparative effects of gonadropin-releasing hormone (GnRH) agonist on the proliferation, apoptosis, and differentiated function of cultured porcine granulosa cells from varying follicle stages. Comparative analyses of porcine granulosa cells from varying follicle stages to respond to GnRH agonist were performed in terms of proliferating cell nuclear antigen (PCNA) expression, occurrence of apoptosis, and 17beta-estradiol (E2) and progesterone (P) secretion. PCNA expression was examined by the avidin/biotin immunoperoxidase method with a monoclonal antibody to PCNA, and apoptosis was assessed by in situ DNA 3'-end labeling method and DNA fragmentation analysis. E2 and P were measured by radioimmunoassays. The PCNA positive rate of granulosa cells cultured in the presence of GnRH agonist (10(-9) M) was lower compared with that of cells cultured in the absence of GnRH agonist. However, the apoptosis positive rate was higher, and E2 and P secretion by cultured granulosa cells was lower in the presence of GnRH agonist (10(-9) M) compared with that in the absence of GnRH agonist. The inhibitory effect of GnRH agonist on PCNA positive rate of cultured cells was prominent in granulosa cells from small and medium but not from large follicles. By contrast, the inhibitory effect of GnRH agonist on E2 and P secretion by cultured cells was prominent in granulosa cells from large but not small and medium follicles. The stimulatory effect of GnRH agonist on apoptosis positive rate of cultured cells was, however, uniform regardless of the stages of follicular growth. These results demonstrate that GnRH agonist exerts diverse actions on granulosa cells over the course of follicular growth. One downregulates granulosa proliferation in immature follicles as well as steroidogenesis in mature follicles, and the other upregulates apoptosis of granulosa cells regardless of the stages of follicular growth.

Uterine leiomyomas appear during the reproductive years and regress after menopause, indicating the ovarian steroid-dependent growth potential. In order to characterize the molecular mechanism of sex steroidal regulation of leiomyoma growth, we examined whether sex steroids could influence the proliferation of leiomyoma cells. As epidermal growth factor (EGF) has been shown to mediate estrogen action and play a crucial role in regulating leiomyoma growth, we also investigated the effects of sex steroids on EGF and EGF receptor (EGF-R) expression in leiomyoma cells. In cultures of leiomyoma cells, the addition of either estradiol (E(2); 10 ng/ml) or progesterone (P(4); 100 ng/ml) resulted in an increase in proliferating cell nuclear antigen (PCNA) expression in the cells, whereas in cultures of normal myometrial cells, the addition of E(2) augmented PCNA expression in the cells, but P(4) did not. Immunoblot analysis revealed that leiomyoma cells contained immunoreactive EGF and that P(4) treatment resulted in an increase in EGF expression in the cells, whereas E(2) treatment resulted in a lower EGF expression in the cells. By contrast, E(2) treatment augmented EGF-R expression in cultured leiomyoma cells, but P(4) did not. These results indicate that P(4) upregulates the expression of PCNA and EGF in leiomyoma cells, whereas E(2) upregulates the expression of PCNA and EGF-R in those cells. It is, therefore, conceivable that P(4) and E(2) act in combination to stimulate the proliferative potential of leiomyoma cells through the induction of EGF and EGF-R expression. We also found that Bcl-2 protein, an apoptosis-inhibiting gene product, was abundantly expressed in leiomyoma relative to that in normal myometrium and that Bcl-2 protein expression in leiomyoma cells was upregulated by P(4), but downregulated by E(2). It seems, therefore, likely that P(4) may also participate in leiomyoma growth through the induction of Bcl-2 protein in leiomyoma cells. The abundant expression of Bcl-2 protein in leiomyoma cells may be one of the molecular bases for the enhanced growth of a leiomyoma relative to that of normal myometrium in the uterus.

Uterine leiomyoma is the most common smooth muscle cell tumor of the myometrium. Estrogen and progesterone (P4) are believed to be physiological regulators of leiomyoma growth. We recently showed that Bcl-2 protein, an apoptosis-inhibiting gene product, was abundantly expressed in leiomyoma relative to its expression in the normal myometrium and that Bcl-2 protein expression in cultured leiomyoma cells was up-regulated by P4, but down-regulated by 17 beta-estradiol (E2). To further characterize the molecular mechanism of sex steroidal regulation of leiomyoma growth, we examined the effect of menstrual phase on proliferating cell nuclear antigen (PCNA) expression in leiomyoma and investigated whether sex steroids could influence PCNA expression in leiomyoma cells cultured under serum-free conditions by immunoblot and immunohistochemical analyses. As epidermal growth factor (EGF) has been shown to mediate estrogen action and to play a crucial role in regulating leiomyoma growth, we also investigated the effects of sex steroids on the expression of EGF and EGF receptor (EGF-R) in cultured leiomyoma cells. The PCNA labeling index in leiomyomas was much greater in the secretory, P4-dominated, phase than in the proliferative phase of the menstrual cycle and was significantly higher than that in the adjacent normal myometrium throughout the menstrual cycle. In monolayer cultures of leiomyoma cells, the addition of either E2 (10 ng/mL) or P4 (100 ng/mL) resulted in an increase in PCNA expression in the cells compared to that in control cultures, whereas in monolayer cultures of myometrial cells, the addition of E2 augmented PCNA expression in the cells, but P4 did not. Immunoblot analysis of proteins extracted from cultured leiomyoma cells revealed that leiomyoma cells contained immunoreactive EGF with a molecular mass of 133 kDa and that the addition of P4 resulted in a remarkable increase in the expression of 133- and 71-kDa immunoreactive EGF in the cells compared to that in control cultures, whereas the addition of E2 resulted in a somewhat lower expression of immunoreactive EGF in the cells. Furthermore, immunocytochemical analysis with a monoclonal antibody to human EGF-R demonstrated that the treatment with E2 augmented EGF-R expression in the cells compared to that in untreated cells, but P4 did not. The concentrations of sex steroids used were within the physiological tissue concentrations found in leiomyomas and myometria. These results indicate that P4 up-regulates the expression of PCNA and immunoreactive EGF in leiomyoma cells, whereas E2 up-regulates the expression of PCNA and EGF-R in those cells. As it is evident that EGF plays a crucial role as a local factor in regulating leiomyoma growth, the P4-induced increase in PCNA expression in leiomyoma cells may be mediated by P4-induced enhanced expression of EGF-like proteins in the cells, whereas the E2-induced increase in PCNA expression in leiomyoma cells may be mediated by E2-induced enhanced expression of EGF-R in those cells. It is, therefore, conceivable that P4 and E2 act in combination to stimulate the proliferative potential of leiomyoma cells through the induction of EGF-like proteins and EGF-R expression in uterine leiomyoma.

Expression of squamous cell carcinoma (SCC) antigen emerged concurrently with squamous formation of the uterine cervix and increased during the neoplastic transformation of the cervical squamous epithelium. SCC antigen expression differed considerably among the histomorphologic cell types of cervical carcinoma. Large cell nonkeratinizing carcinoma contained high levels of the antigen. In contrast, no appreciable expression of SCC antigen was observed in small cell nonkeratinizing carcinoma. The pattern of SCC antigen expression closely coincided with EGF receptor (EGF-R) expression in cervical squamous neoplasia. This suggests that the expression of SCC and EGF-R in cervical carcinoma is related to the differentiation or dedifferentiation processes of the tumor cells. SCC production by CaSki cervical epidermoid carcinoma cells was stimulated by EGF. It seems likely that an autocrine system, in which EGF serves as the signal, may exist in cervical squamous carcinoma. 17beta-estradiol and L-triiodothyronine were found to upregulate EGF-R expression, proliferative potential and SCC production in the CaSki cervical carcinoma cells.

Uterine leiomyoma is the most common benign smooth muscle cell tumor of the myometrium. Although Bcl-2 protein is known to be an apoptosis-inhibiting gene product and to prevent apoptotic cell death in a variety of cells, there are no published data regarding whether human leiomyomas express Bcl-2 protein. In the present study, we examined the expression of Bcl-2 protein in leiomyomas in comparison with that in the normal myometrium using an immunohistochemical method and immunoblot analysis with a monoclonal antibody to human Bcl-2 protein. Furthermore, we investigated whether sex steroid hormones could influence the levels of Bcl-2 protein expression in leiomyoma cells cultured in vitro under serum-free, phenol red-free conditions. Immunohistochemical staining for Bcl-2 protein was prominent in leiomyoma cells, but was scarcely present in normal myometrial smooth muscle cells. The expression of Bcl-2 protein in leiomyoma cells was most abundant in the secretory, progesterone-dominated, phase of the menstrual cycle, but was less abundant in the proliferative phase of the menstrual cycle. Western blot analyses of leiomyoma and myometrium tissue extracts revealed that Bcl-2 protein, with a molecular mass estimated at approximately 26 kDa, was abundantly present in leiomyoma tissue extracts, but was undetectable in normal myometrial tissue extracts. In monolayer cultures of uterine leiomyoma cells under a serum-free condition, the addition of progesterone (100 ng/mL) resulted in a striking increase in Bcl-2 protein expression in the cultured leiomyoma cells relative to that in control cultures, whereas the addition of 17 beta-estradiol (10 ng/mL) resulted in a reduction in Bcl-2 protein expression in the cells. The concentrations of sex steroids used were within the physiological tissue concentrations found in leiomyomas and myometrium. The present results suggest that the abundant expression of Bcl-2 protein may have a molecular basis characteristic of leiomyomas in the human uterus and that progesterone may play a vital role in the enhanced expression of Bcl-2 protein in human uterine leiomyoma cells.

The cytologic localization and cellular levels of insulin-like growth factor binding protein-4 (IGFBP-4) in follicular and stromal compartments of normal and polycystic ovary syndrome (PCOS) ovaries during follicular growth and regression were investigated by the avidin/biotin immunoperoxidase method with a polyclonal antibody to human IGFBP-4, and a comparative assessment of IGFBP-4 expression in normal and PCOS ovaries was provided. In normal human ovaries, IGFBP-4 was immunolocalized to the oocyte throughout follicular growth, while the surrounding granulosa and theca cells were negligible for IGFBP-4 immunostaining in primordial, preantral and antral follicles. IGFBP-4 immunostaining became apparent, however, in the lutein cells of corpora lutea and the granulosa and theca cells of atretic follicles. In PCOS ovaries, prominent immunostaining for IGFBP-4 was apparent not only in the oocyte, but also in the surrounding granulosa cells in preantral follicles. In antral follicles from PCOS women without hyperinsulinemia, IGFBP-4 immunostaining was more prominent in the granulosa cells than the theca cells, whereas in antral follicles from PCOS women with hyperinsulinemia IGFBP-4 immunostaining was more prominent in the theca cells than the granulosa cells. Furthermore, in atretic follicles within PCOS ovaries IGFBP-4 immunostaining was prominent in the theca cells, regardless of the association of hyperinsulinemia. These results demonstrate for the first time that there is a great difference in cellular expression of IGFBP-4 between normal and PCOS human ovaries. In light of the high affinity of IGFBP-4 for IGF-1, the abundant expression of IGFBP-4 in granulosa and theca cells of preantral and antral follicles of PCOS ovaries may lead to decreases in the bioavailability of IGF-I in those follicles. The decrease in IGF-I-mediated stimulation of gonadotropin actions on granulosa and theca cells in preantral and antral follicles may impair the induction of aromatase activity, causing an androgenic microenvironment which is characteristic of atretic follicles and PCOS follicles.

In order to elucidate the role of insulin-like growth factor-I (IGF-I) in human placental growth and function, the effects of IGF-I on the proliferation and differentiation of trophoblasts were investigated using an organ culture system of early placental tissues. Explants of trophoblastic tissues obtained from 4-5-week or 6-12-week placentae were, respectively, cultured with or without IGF-I, in a serum-free condition. The effect of IGF-I on the proliferative activity of trophoblasts was examined by immunocytochemical techniques with a monoclonal antibody to proliferating cell nuclear antigen (PCNA), while the effect of IGF-I on the differentiated function of trophoblasts was assessed by determining the ability to secrete human chorionic gonadotropin (hCG) and human placental lactogen (hPL). In 4-5-week placentae, IGF-I and IGF-I receptor were almost exclusively localized in cytotrophoblasts and IGF-I augmented the proliferative activity of cytotrophoblasts without affecting the ability to secrete hCG and hPL. By contrast, in 6-12-week placentae, IGF-I and IGF-I receptor were localized in both cytotrophoblasts and syncytiotrophoblasts and IGF-I stimulated the secretion of hCG and hPL following the enhancement of the proliferative activity of trophoblasts. In column chromatography of the serum-free medium obtained following 5-day culture of early placental tissues, an elution peak of immunoreactive IGF-I was found in the fractions similar to the elution region of [125I]IGF-I. These findings suggest that IGF-I acts as an autocrine/paracrine factor in regulating early placental growth and function.

The cytologic localization and cellular levels of TGF alpha in the human ovary during follicular growth and regression were examined by avidin/biotin immunoperoxidase techniques with a monoclonal antibody to TGF alpha. In primordial follicles, only the oocyte showed intense immunostaining for TGF alpha, whereas the flattened pregranulosa cells were negative for the immunostaining. The earliest stage of follicular growth at which immunostaining for TGF alpha in granulosa cells and theca interna cells became apparent was the preantral stage. With the increase in the size of follicles, the intensity of TGF alpha immunostaining in the oocyte decreased, whereas the staining intensity of the granulosa and theca cells increased. The immunostaining for TGF alpha in granulosa and theca interna cells persisted in the corpus luteum, and further intensified during the midluteal phase. In the regressing corpus luteum, the immunostaining was present only in the peripheral theca lutein cells adjacent to the central scar tissue. The corpus albicans was negative for the immunostaining. Stromal cells exhibited weak staining for TGF alpha. In atretic follicles, the theca interna cells exhibited intense staining for TGF alpha without appreciable staining in the scattered granulosa cells. This is the first report to demonstrate that TGF alpha expression in the oocyte is maximal in primordial follicles, whereas TGF alpha expression in granulosa and theca cells increases with the progress of follicles and reaches its maximum in the lutein cells during the mid luteal phase.(ABSTRACT TRUNCATED AT 250 WORDS)

The cytologic localization and cellular levels of insulin receptors in the human ovary during follicular growth, regression and atresia were examined by the avidin/biotin immunoperoxidase techniques with a monoclonal antibody to insulin receptor. In primordial follicles, only the oocyte showed a weak immunostaining for insulin receptor, whereas the stromal cells surrounding primordial follicles were moderately immunostained. The earliest stage of follicular growth at which immunostaining for insulin receptor in granulosa cells and theca interna cells became apparent was the preantral stage. With the increase in the size of the follicles, the immunostaining of the oocyte and follicular elements intensified, whereas the staining intensity of the stromal cells surrounding growing follicles was reduced compared to those surrounding primordial follicles. The immunostaining in granulosa and theca interna cells persisted in the corpus luteum, and further intensified during the midluteal phase. In the regressing corpus luteum, the immunostaining was present only in the peripheral lutein cells adjacent to the central scar tissue. The corpus albicans was negative for the immunostaining, but the surrounding stromal cells exhibited predominant staining. In atretic follicles, the theca interna cells exhibited intense staining for insulin receptor without appreciable staining in the scattered granulosa cells, whereas the surrounding stromal cells were moderately immunostained. This is the first study to demonstrate notable changes in insulin receptor expression in the oocyte, granulosa cells, theca cells, lutein cells and surrounding stromal cells during follicular growth, regression and atresia. The results obtained indicate insulin participation in oocyte maturation, follicular growth and stromal cell function. The increased expression of insulin receptors in theca interna cells of atretic follicles and in stromal cells surrounding the corpora albicans raises the intriguing possibility of insulin involvement in the transformation of theca interna cells into stromal cells. This implies that insulin may participate in remodelling ovarian local tissues following follicular atresia and luteolysis in the human ovary.

In the ovary, insulin and insulin-like growth factor-I (IGF-I) act synergistically with FSH to augment estrogen production by granulosa cells and with LH to augment androgen production by thecal stromal cells. It is also evident that insulin resistance is common in patients with polycystic ovary syndrome (PCO). Thus, in the present study we investigated the expression of insulin and IGF-I receptors in PCO ovaries and compared them with those in normal ovaries. Ovarian tissues were obtained from four PCO patients undergoing wedge resection, and from six patients who underwent radical hysterectomy. Immunohistochemical staining for insulin and IGF-I receptors was performed by avidin/biotin immunoperoxidase techniques. In normal ovaries, the expression of insulin and IGF-I receptors in follicular compartment became apparent in the preantral follicle stage and augmented with the follicular growth, while the stromal cells, regardless of the follicle stage, possessed insulin and IGF-I receptors. In PCO ovaries associated with hyperinsulinemia, no expression of insulin receptors was detected in granulosa or thecal stromal cells, while IGF-I receptor expression increased in thecal stromal cells but decreased in granulosa cells compared to those in normal ovaries. However, in PCO ovaries from patients without hyperinsulinemia, insulin receptor expression was apparent in both granulosa and thecal stromal cells, with a similar intensity to that observed in normal ovaries, while IGF-I receptor expression was negligible in granulosa cells but sustained in thecal stromal cells. These findings suggest that decreased expression of insulin receptors in PCO ovaries associated with hyperinsulinemia may be secondary to receptor down regulation, whereas defective expression in granulosa cells along with elevated or persisted expression in thecal stromal cells of IGF-I receptors may be common in PCO ovaries and contribute to the endocrine profiles of PCO in which varying degrees of hyperandrogenism is a predominant feature.

Two cases of myocarditis, who had suffered from ventricular extrasystole, leucocytosis and elevated serum enzyme for a long period died from congestive heart failure and/or arrhythmias. The biopsy specimens from the right ventricle in one of them showed a positive reaction against Coxsackie B virus (1, 3, 4 and 5) in the fluorescent antibody method. One case of virus pericarditis had 5 recurrences over a five-year period. He suffered from dyspnea, chest oppression and general fatigue at each recurrence. Cardiomegaly on a chest X-ray, electrocardiographic abnormalities, leucocytosis and elevated serum enzyme appeared. However, serum neutralizing antibody titers against Coxsackie B2 had not risen significantly except during the first attack. Interferon administration inhibited its recurrence successfully.

We present the first case of retroperitoneal alveolar soft part sarcoma (ASPS) to be reported in Japan. The patient was a 27-years-old woman. After the retroperitoneal (tumors were) removed, bilateral lung metastasis was found and removed. Shortly thereafter, a recurrent retroperitoneal tumor arose, but because removal of the tumor was impossible, injection of 100 mg of cisplatin and 100 mg of adriamycin into the feeding artery was performed, and radiotherapy was also undertaken. However, the treatments were not effective, and the patient is now being followed on an outpatient basis.

The estrogen receptor was assayed in 8 intracranial meningiomas, 14 lung cancers, 3 thymomas and 2 malignant lymphomas using the dextran-charcoal method. Progesterone and androgen receptors were also assayed in all the cases of lung cancer. The estrogen receptor assay was positive in 3 meningiomas, 2 lung cancers, and all thymomas and malignant lymphomas. The androgen receptor assay was positive in one case of lung cancer but the progesterone receptor was negative in all assayed cases. No cases showed multiple receptor positivity. An antiestrogen (tamoxifen) was administered to one case each of intracranial meningioma and lung cancer with positive estrogen receptor. The receptor content was decreased to an undetectable level in the former after 4 months of administration. This finding suggests the estrogen dependency of the tumor. The lung cancer patient, however, died 2 weeks later without any evidence of hormone dependency.

A case of breast cancer containing osteoclast-like multinucleated giant cells was examined cytologically, light and electron microscopically to find morphological evidences suggesting the origin of the giant cells. There were multiple evidences showing the same carcinomatous origin of each cells including osteoclast-like multinucleated giant cells.